In September of 1966 I was given an oral glucose tolerance test to determine my susceptibility to ‘juvenile diabetes,’ as it was called at the time, and the test result was negative. But then, just a month later, I was diagnosed with the disease, so at least in my case, there must have been very little accumulation of hyperglycemic damage before I was found to have delayed nerve conduction velocities, suggesting either that miniscule excesses of glucose can already produce measurable damage, or that other factors are involved in causing the complications of type 1 diabetes, such as the continuation of the same autoimmunity that causes the beta cell destruction, or genetic influences inherited along with the cluster of genes that determine susceptibility to type 1 diabetes.
B. Fierro, et al., “Nerve Conduction Velocity and Circulatory Immunocomplexes in Type 1 Diabetic Children,” Acta Neurologica Scandinavica, 83 (3) 176-178 (1991) and N. Janahi, et al., “Diabetic Peripheral Neuropathy. Is It an Autoimmune Disease?” Immunology Letters, 106 (1) 73-76, among others, suggest that diabetic nerve disease may be caused by the same autoimmune processes which cause the beta cell destruction, which would explain the results in Donna Younger’s experiment which found slowing of nerve conduction velocities in newly-diagnosed patients despite the minimal impact of hyperglycemia when these patients presented.
S. Yigit, et al., “Association of MTHFR Gene C6777 Mutation with Diabetic Peripheral Neuropathy and Diabetic Retinopathy,” Molecular Vision, 19, 1626-1630 (2013) and J. Hoeijmakers, et al., “Channelopathies, Painful Neuropathy, and Diabetes: Which Way Does the Causal Arrow Point?” Trends in Molecular Medicine, 20 (10) 544-550 (2014), among others, suggest that genes inherited along with those inducing the susceptibility to type 1 diabetes may also cause diabetic neuropathy, which would also explain why the group of patients I was with in 1966 was found to have measurably slowed nerve conduction velocity even though we had had very little exposure to hyperglycemia.
In staging studies of the development of type 1 diabetes, in the first prodromal stage the appearance of autoimmune antibodies has been found a good 5 years prior to the diagnosis of the disease. However, only in the second stage has an abnormal response to a glucose tolerance test been found, meaning that while these patients do not yet have frank hyperglycemia, they do show it after an intense glucose challenge, meaning that they might be showing hyperglycemia after binging on sweets in this period. In fact, their HbA1c values can be very slightly elevated in this period, from 10% to 20% higher than normal, which is still a very low level. The duration of their exposure in the second stage before the disease appears is quite short, since it has been found that the “2-h [hour] OGTT [oral glucose tolerance test] glucose levels … did not begin to change until approximately 0.8 years before diagnosis … .” (Richard Insel, et al., “Staging Presymptomatic Type 1 Diabetes,” Diabetes Care, 38 (10) 1964-1974 (2013)).
What this all means is that insofar as there is any burden of hyperglycemia on the patient before diagnosis of type 1 diabetes, it is very small and very brief, so that if even this small amount of hyperglycemia can cause measurable damage, patients with established cases of type 1 diabetes would have to achieve an impossibly meticulous degree of control to avoid complications.